J Pharmacol Exp Ther. 1981 Jun;217(3):602-10.
Radioimmunoassay and pharmacokinetic profile of bupropion in the dog.

Butz RF, Schroeder DH, Welch RM, Mehta NB, Phillips AP, Findlay JW.

A radioimmunoassay (RIA) procedure for the quantification of bupropion (dl-2-tert-butylamino-3'-chloropropiophenone) in biological fluids is described. Immunization of rabbits with conjugates of bovine serum albumin and p-succinoyl propylbupropion or p-carbomethoxybupropion resulted in the production of antisera which are capable of detecting less than 1 ng ml-1 (100 pg actual mass) of bupropion in the RIA, utilizing [6-3H] bupropion as radioligand. The antisera used in these studies have low cross-reaction (approximately 0.1% or less) with known side chain metabolites of bupropion, but exhibit significant cross-reaction with p-hydroxybupropion (30.3%). Excellent agreement was obtained between RIA and high-pressure liquid chromatography determinations of bupropion concentrations in human plasma samples, but plasma or serum from bupropion-treated dogs, rats and mice required extraction from basic medium to remove some interference before RIA. The assay was applied to a study of bupropion disposition in two beagles of each sex after i.v. and p.o. administrations of bupropion hydrochloride (100 mg). The pharmacokinetic profile in dogs was best described by an open two-compartment model after either route of drug administration. Peak plasma bupropion levels after oral dosing were highly variable, ranging from 12.9 to 63.5 ng ml-1 at 26 to 32 min after drug administration. The mean terminal phase half-life of bupropion was calculated to be 1.73 hr after either route and the absolute oral bioavailability of the drug varied from 2.0 to 6.5%.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6785419&dopt=Abstract Bupropion Wellbutrin




Eur J Clin Pharmacol. 1981;21(2):127-35.
Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects.

Findlay JW, Van Wyck Fleet J, Smith PG, Butz RF, Hinton ML, Blum MR, Schroeder DH.

The pharmacokinetics of bupropion hydrochloride, a structurally novel antidepressant agent, have been studied in healthy male and female subjects following administration of single oral doses of 50, 100 and 200 mg. Plasma drug concentrations were determined directly by a specific radioimmunoassay (r.i.a.), while urinary measurements required a prior solvent extraction to remove substances interfering in the assay. Bupropion appeared rapidly in the plasma, suggesting good absorption. Drug plasma concentration-time data were fitted well to a two-compartment open model of drug disposition by use of the computer program NONLIN. By comparison of AUC, Cmax and tmax values, the pharmacokinetics of bupropion were found to be linear across the 50-200 mg dose range in both sexes. When the data were normalized for subjects' body weights, no differences between pharmacokinetic parameters for male and female subjects were found. Mean disposition half-lives across treatments were 1.2-1.4 h for t1/2 alpha and 10.7-13.8 h for the t1/2 beta. Bupropion was extensively bound (85%) to human plasma proteins over a wide drug concentration range. Less than 1% of a 200 mg oral dose of bupropion hydrochloride appeared in the urine of 16 subjects as unchanged drug, indicating extensive metabolism of the parent compound.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6804243&dopt=Abstract Bupropion Wellbutrin




Am J Psychiatry. 1991 Apr;148(4):512-6.
Cardiovascular effects of bupropion in depressed patients with heart disease.

Roose SP, Dalack GW, Glassman AH, Woodring S, Walsh BT, Giardina EG.

New York State Psychiatric Institute, New York.

OBJECTIVE: The cardiovascular effects of therapeutic plasma levels of tricyclic antidepressants in depressed patients with and without preexisting cardiac disease have been well characterized and include orthostatic hypotension and conduction delay. Bupropion, structurally unrelated to tricyclic antidepressants, is relatively free of cardiac side effects in depressed patients without cardiac disease. However, it is unknown whether bupropion is safe for depressed patients with preexisting heart disease, so the authors studied the cardiovascular effects of bupropion in such patients. METHOD: The subjects were 36 inpatients with DSM-III major depression and preexisting left ventricular impairment (N = 15), ventricular arrhythmias (N = 15), and/or conduction disease (N = 21). The patients continued their cardiac drug regimens and received bupropion for 3 weeks (mean +/- SD dose = 442 +/- 47 mg/day). Cardiovascular functioning was measured by pulse, blood pressure, high-speed ECG, 24-hour portable ECG, and radionuclide angiography. RESULTS: Although bupropion caused a rise in supine blood pressure, it did not cause significant conduction complications, did not exacerbate ventricular arrhythmias, had a low rate of orthostatic hypotension, and had no effect on pulse rate. However, bupropion treatment was discontinued for 14% of the patients because of adverse effects, including exacerbation of baseline hypertension in two patients. CONCLUSIONS: The cardiovascular profile of bupropion may make this drug a useful agent in the treatment of the depressed patient with preexisting cardiovascular disease. Further studies, with longer durations of bupropion treatment and more subjects, are needed to confirm these findings.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1900980&dopt=Abstract Bupropion Wellbutrin




J Pharm Pharmacol. 1990 Nov;42(11):799-801.
Phenytoin-bupropion interaction: effect on plasma phenytoin concentration in the rat.

Tekle A, al-Khamis KI.

Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Kingdom of Saudi Arabia.

The effect of coadministration of bupropion (50 mg kg-1, p.o.) on the disposition profile of phenytoin has been studied in the rat. Plasma phenytoin concentration was measured serially for 10 h by HPLC. Bupropion had little or no effect on the pharmacokinetic parameters of an acutely administered dose of phenytoin. Following multiple doses of phenytoin however (i.e. steady state) the coadministration of bupropion resulted in significant increases in the elimination half-life (t 1/2), the area under the plasma concentration-time curve (AUC) and the time to maximum plasma concentration (tmax). Allowing for the limitations of single dose studies, these results point to a possible pharmacokinetic interaction between bupropion and phenytoin--the clinical significance of which needs to be assessed.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1982306&dopt=Abstract Bupropion Wellbutrin




Pharmacopsychiatry. 1990 Jul;23(4):187-94.
Antidepressant profile of bupropion and three metabolites in mice.

Martin P, Massol J, Colin JN, Lacomblez L, Puech AJ.

Departement de Pharmacologie, Faculte de Medicine Pite-Salpetriere, Paris, France.

Bupropion is a novel antidepressant, distinct from tricyclic antidepressants both neurochemically and behaviorally. Bupropion forms several metabolites in both rodents and humans. Three chemically different molecules - BW 306, BW 494, and BW 287 - were selected. Comparative assessment of antidepressant activity of bupropion and its metabolites in mice, and pharmacological analysis of possible mechanisms of action of the parent drug and its metabolites (using interaction studies with pimozide, D,L-propranolol, and prazosin) were carried out. The results obtained show that: bupropion has a pharmacological spectrum in various animal models which predicts both antidepressant and stimulatory activity in man. BW 306 is the most active of the metabolites studied and, compared to bupropion, seems more "antidepressant" and less stimulant. BW 494, compared to bupropion or BW 306, has a lower degree of activity in various tests used to evaluate antidepressants. BW 287 has no effect in any of the tests used in this study. The interaction studies with pimozide, D,L-propranolol, and prazosin in the various tests have shown that: the stimulatory effect of bupropion, BW 306, and BW 494 is antagonized by both pimozide and prazosin. in the behavioral despair test, the reduction in the duration of immobility by bupropion and BW 494 is antagonized by pimozide, but not by prazosin or D,L-propranolol. the antagonism of reserpine-induced hypothermia by bupropion and BW 306 is significantly decreased by prazosin and D,L-propranolol, but not by pimozide. These data suggest that the clinical antidepressant profile (without a major stimulatory effect) observed in man after administration of bupropion is related to metabolite BW 306 and possibly to BW 494, rather than t




J Clin Psychopharmacol. 1990 Oct;10(5):328-32.
Disposition of bupropion in healthy volunteers and subjects with alcoholic liver disease.

DeVane CL, Laizure SC, Stewart JT, Kolts BE, Ryerson EG, Miller RL, Lai AA.

Department of Pharmacy Practice, University of Florida, Gainesville 32610.

Bupropion hydrochloride is a new monocyclic antidepressant. In humans, its disposition results in the formation of three major metabolites: the morpholinol metabolite, the erythroamino alcohol, and the threoamino alcohol metabolite. Bupropion's disposition was monitored following a single oral 200 mg dose in eight healthy volunteers and eight age- (44.5 +/- 8.4 years) and weight- (77.4 +/- 6.7 kg) matched volunteers with alcoholic liver disease. This latter group is of interest because the incidence of depression is more frequent in alcoholics than in the general population, and the liver is the major route of elimination for cyclic antidepressants. The mean elimination half-life of the morpholinol metabolite was significantly prolonged in subjects with alcoholic liver disease (32.2 +/- 13.5 vs. 21.1 +/- 4.9 hours (p less than 0.05), while the differences in bupropion (17.3 +/- 8.6 hours vs. 16.5 +/- 10.4 hours for healthy subjects and subjects with alcoholic liver disease, respectively), erythroamino alcohol (26.1 +/- 13.3 hours vs. 29.8 +/- 6.9 hours for healthy subjects and subjects with alcoholic liver disease, respectively), and threoamino alcohol (25.5 +/- 8.6 hours vs. 23.4 +/- 10.7 hours for healthy subjects and subjects with alcoholic liver disease, respectively) were minimal. Mean area under the plasma concentration time curves for bupropion and metabolites were increased in subjects with alcoholic liver disease; however, clear differences between means of these small groups did not emerge, probably due to the increased variability of bupropion pharmacokinetics in these subjects. As a therapeutic agent for the treatment of depression in chronic alcoholics who may consume alcohol in combination with their